Mi-2/NuRD complex

In the field of molecular biology, the Mi-2/NuRD (Nucleosome Remodeling Deacetylase) complex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities.[1][2] As of 2007, Mi-2/NuRD was the only known protein complex coupling chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.[3]

The NuRD complex contains seven subunits: the histone deacetylase core proteins HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, the metastasis-associated proteins MTA1 (or MTA2 / MTA3), the methyl-CpG-binding domain protein MBD3 (or MBD2) and the chromodomain-helicase-DNA-binding protein CHD3 (aka Mi-2alpha) or CHD4 (aka Mi-2beta).

The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes.[4][5]

Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency, [6] that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). [7]

References

  1. ↑ Xue Y, Wong J, Moreno GT, Young MK, Côté J, Wang W (1998). "NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.". Mol Cell 2 (6): 851–61. doi:10.1016/S1097-2765(00)80299-3. PMID 9885572.
  2. ↑ Zhang Y, Yinghua L (2010). "The Expanding Mi-2/NuRD Complexes: A Schematic Glance". Proteomics Insights 3: 79–109. doi:10.4137/PRI.S6329.
  3. ↑ Denslow, SA; Wade, PA. "The human Mi-2/NuRD complex and gene regulation". Oncogene 26: 5433–8. doi:10.1038/sj.onc.1210611. PMID 17694084.
  4. ↑ Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.". Genes Dev 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
  5. ↑ Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D. (1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.". Cell 95 (5): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534.
  6. ↑ Luo, M., et al & Tao, W., Lu, Z., Grummt, I. (2013), NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells. STEM CELLS, 31: 1278–1286. doi: 10.1002/stem.1374
  7. ↑ Yoach Rais, Asaf Zviran, Shay Geula, et al. (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature, doi:10.1038/nature12587
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